DESCRIPTION (Applicant's abstract) Dr. Sally Campbell-Lee is an African-American physician who has completed fellowship training in Transfusion Medicine, and will be the principal investigator on this award. Drs. Paul Ness and William Baldwin, both of the Department of Pathology at Johns Hopkins, will serve as co-mentor and primary mentor, respectively. The clinical and research programs at Johns Hopkins Medical Institutions provide a rich environment for the growth and development of young investigators, with many resources at their disposal. Dr. Campbell-Lee's career goals are to become an independent investigator specializing in immune mechanisms of allo-immunization in transfusion in transfusion, in addition to serving as a medical director of a hospital blood bank and transfusion medicine service. This award will aid in reaching this goal by providing Dr. Campbell-Lee' with additional training in immunological research methods, and the use of animal models in examining mechanisms of alloimmunization, the application of which will provide insight into a longstanding problem in transfusion medicine, that of immune modulation in the transfusion recipient. The research project will investigate immune mechanisms of red cell alloimmunization in transfusion. When red blood cells (rbc) are transfused, the recipient may become alloimmunized to foreign red cell antigens. When alloimmunization occurs, the specificity of the antibody must be identified, and blood must be found that lacks the corresponding antigen for that patient. This is labor intensive and costly, and can cause a significant delay in the availability of blood. In order to develop prevention or treatment for this problem, immune mechanisms regulating antibody formation must be better identified. We will study the following using a murine transfusion system: the effects of eliminating or modifying targeted subpopulations of donor white blood cells alloimmunization to rbc antigens; the effect of coating rbc for transfusion with C3d on alloantibody formation, and the effect on red cell alloantibody formation of modifying antigen presenting cells by blockage of the CD28-B7 co-stimulatory pathway with CTLA41g.